title: Three distinct phases of HIV-1 RNA decay in treatment-naive patients receiving raltegravir-based antiretroviral therapy: ACTG A5248.
abstract: OBJECTIVE
  The goal of this study was to define viral kinetics after initiation of raltegravir (RAL)-based antiretroviral therapy (ART).
  
  
  METHODS
  ART-naive patients received RAL, tenofovir disoproxil fumarate, and emtricitabine for 72 weeks. Human immunodeficiency virus type 1 (HIV-1) RNA were measured by ultrasensitive and single-copy assays, and first (d1)-, second (d2)-, and, third (d3)-phase decay rates were estimated by mixed-effects models. Decay data were compared to historical estimates for efavirenz (EFV)- and ritonavir/lopinavir (LPV/r)-based regimens.
  
  
  RESULTS
  Bi- and tri-exponential models for ultrasensitive assay (n = 38) and single-copy assay (n = 8) data, respectively, provided the best fits over 8 and 72 weeks. The median d1 with ultrasensitive data was 0.563/day (interquartile range [IQR], 0.501-0.610/day), significantly slower than d1 for EFV-based regimens [P < .001]). The median duration of d1 was 15.1 days, transitioning to d2 at an HIV-1 RNA of 91 copies/mL, indicating a longer duration of d1 and a d2 transition at lower viremia levels than with EFV. Median patient-specific decay estimates with the single-copy assay were 0.607/day (IQR, 0.582-0.653) for d1, 0.070/day (IQR, 0.042-0.079) for d2, and 0.0016/day (IQR, 0.0005-0.0022) for d3; the median d1 duration was 16.1 days, transitioning to d2 at 69 copies/mL. d3 transition occurred at 110 days, at 2.6 copies/mL, similar to values for LPV/r-based regimens.
  
  
  CONCLUSIONS
  Models using single-copy assay data revealed 3 phases of decay with RAL-containing ART, with a longer duration of first-phase decay consistent with RAL-mediated blockade of productive infection from preintegration complexes.
authors.affiliation: The Johns Hopkins University, Baltimore, Maryland 21205, USA. aandrade@jhmi.edu
authors.forename: Adriana
authors.initials: A
authors.lastname: Andrade
authors.forename: Susan L
authors.initials: SL
authors.lastname: Rosenkranz
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Cillo
authors.forename: Darlene
authors.initials: D
authors.lastname: Lu
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Michael
authors.initials: M
authors.lastname: Lederman
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
authors.forename: Thomas
authors.initials: T
authors.lastname: Campbell
authors.forename: Judith
authors.initials: J
authors.lastname: Feinberg
authors.forename: Charles
authors.initials: C
authors.lastname: Flexner
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D061466:Lopinavir / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D010865:Pilot Projects; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000627:therapeutic use*; D020871:RNA Stability / Q000187:drug effects*; D012367:RNA, Viral / Q000378:metabolism; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000627:therapeutic use; D000068698:Tenofovir; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D011760:Pyrrolidinones; D012367:RNA, Viral; D061466:Lopinavir; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D000225:Adenine; C098320:efavirenz; D019438:Ritonavir
keywords: ACTG A5160s; ACTG A5166s; ACTG A5248; Roche ultrasensitive assay; raltegravir; single copy assay; viral decay